Synthesis of 7-Epi +-FR900482: an epimer of comparable anti-cancer activity

Org Lett. 2008 Apr 3;10(7):1369-72. doi: 10.1021/ol800127a. Epub 2008 Mar 5.

Abstract

FR900482 is a potent anti-tumor therapeutic that has been investigated as a replacement candidate for the clinically useful Mitomycin C. Herein, we report synthesis and biological testing of 7-Epi (+)-FR900482, which demonstrates equal potency relative to the natural product against several cancer cell lines. Highlights of this work include utilization of our palladium-catalyzed DYKAT methodology and development of a Polonovski oxidative ring expansion strategy to yield this equipotent epimer in 23 linear steps.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Oxazines / chemical synthesis
  • Oxazines / chemistry
  • Oxazines / pharmacology
  • Stereoisomerism

Substances

  • 7-epi-FR900482
  • Antineoplastic Agents
  • Oxazines
  • FR 900482